We read with interest the elegant work by Park et al. (1) assessing the optimal left main (LM) minimal lumen area (MLA) criteria to identify hemodynamically significant stenoses. Due to the potential major clinical implications of these findings, some relevant issues should be addressed. First, the LM-MLA cutoff value seems to be population dependent. A previous U.S. study yielded a cutoff value of 5.9 mm2 (sensitivity, 93%; specificity, 94%) for a fractional flow reserve (FFR) <0.75 (2). The average LM-MLA in the patients included in these 2 studies was strikingly different (7.6 mm2 in the U.S. study and 4.8 mm2 in the Korean study). The most plausible explanation for such differences appears to be ethnicity related. Another recent study compared coronary LM lesions between 99 white North American and 99 Asian patients (3). Again, Asian patients had a significantly smaller LM-MLA (5.2 ± 1.8 mm2 vs. 6.2 ± 1.4 mm2; p < 0.0001). Accordingly, we believe that the attempts by Park et al. (1) to adjust for body mass index in their series of 112 Asian-only patients cannot exclude this important influence. Second, given the unique prognostic implications of LM-derived ischemia, the optimal cutoff value must show very high sensitivity and negative predictive values. This is the case for a cutoff value of 6 mm2(1,2). In a previous study (4), we found that in patients with an LM-MLA ≥6 mm2, revascularization could be safely deferred. Moreover, we suggested that in patients with LM-MLAs of 5 to 6 mm2, clinical decisions should be individualized or, even better, informed with the FFR if feasible. In the current study (1), the sensitivity (77%) and negative predictive value (75%) for a 4.5-mm2 cutoff value were clearly suboptimal. Notably, among the 54 lesions with an LM-MLA >4.5 mm2, 13 (24.1%) had an FFR of ≤0.80. We honestly believe that missing 1 in 4 patients with severe ischemia is not justified in this challenging scenario. Third, a theoretical LM-MLA cutoff value may be nicely derived from fractal geometry. A study confirmed that the linear law was more exact in this regard than Murray’s law, which largely underestimated the calculated mother vessel diameter (5). Using the currently established 3 mm2 as the best cutoff value of MLA for the LM branches (6), the calculated LM-MLA cutoff value by linear law is 5.8 mm2. Fourth, the optimal LM-MLA cutoff value should be prospectively validated. In the LITRO (4), a prospective multicenter study including 354 patients, the 6-mm2 cutoff value was clinically validated. At 2 years, the outcome of deferred patients was equivalent to that of the revascularized group. Importantly, the outcome of the few patients with 5- to 6-mm2 LM-MLA who did not undergo revascularization was significantly worse. Last but not least, the LM-MLA cutoff value is just aimed to exclude the presence of current ischemia. However, 36% of patients in the study by Park et al. (1) with “isolated” LM disease presented as an acute coronary syndrome, and on intravascular ultrasound, plaque ruptures (30.6%) and intracoronary thrombi (33.3%) were readily observed. It is difficult to believe that the fate of these unstable plaques may be only dictated by the hemodynamic significance encountered at the time of the examination.

We strongly believe that the provocative proposal of 4.5 mm2 as an LM-MLA optimal cutoff value should be taken very cautiously until further clinical data support its prognostic validity.

Footnotes

Please note: Dr. de la Torre Hernández has received research grants from Abbott Vascular, Boston Scientific, Biosensors, St. Jude Medical, and Biotronik; and honoraria for serving on the advisory board and Speakers Bureau of Abbott Vascular, Boston Scientific, Biosensors, St. Jude Medical, Biotronik, Volcano, Lilly, and AstraZeneca. Drs. Hernandez and Alfonso have reported that they do not have any relationships relevant to the contents of this paper to disclose.